Analysis for Carom complex, signaling and function by database mining

Carom is a novel protein that regulates membrane curvature and transmits pathophysiological signaling. The tissue expression of Carom is unclear and its functional role and signaling are unknown. We employed a group of combined database mining strategies and established a working model of Carom signaling. We identified 26 Carom partners and established their expression profiles in human and mouse tissues. We classified three tiers of tissues for Carom/partner expression and found lymph node was the tier 1 tissue expressing Carom and most of its partners. Using GEO database, we discovered that four conditions (hypoxia, endometriosis, PPARγ deletion and iPSC reprogramming) altered Carom/partner expression in endothelial cells. We identified 26 Carom partner signalings by Ingenuity pathway analysis. Ten of the 26 pathways and three genes (ITSN1, UBC and HSPA5) were reported to be regulated in the above four conditions. Paired induction of Carom/ITSN1 elevation was associated with pathological angiogenesis. Whereas, paired reduction of Carom/HSPA5 or UBC was associated with iPSC generation. These results provide an insight on identifying Carom complex model and predicting its functional implications.